ABSTRACT
Division of Geriatrics and Gerontology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
BACKGROUND OR INTRODUCTION
Skeletal muscle is the major site of both insulin and exercise mediated glucose disposal. Muscle also plays a major role in the whole body insulin resistance associated with central/visceral obesity, that is the major cause of type II diabetes. Glucose transport across the sarcolemma is the primary rate-limiting step in glucose metabolism in muscle under most physiological and pathophysiological conditions. Studies on intact humans and laboratory animals are necessary for understanding how glucose metabolism is regulated under physiological conditions. However, glucose delivery via the circulation can limit glucose uptake by muscle in vivo under some of the extreme conditions that are necessary for investigation of the mechanisms involved in the regulation of glucose transport. These include measurement of maximal insulin responsiveness and the additive effects of maximally effective insulin and contraction stimuli. Although these conditions never occur normally in vivo, they have to be studied to provide an understanding of how glucose transport is regulated. Furthermore, in experiments dealing with the effects of various inhibitors and activators, in which glucose is delivered via the circulation, one can not be sure that the agent under study is acting on glucose transport rather than on blood flow and glucose delivery. In infusion studies on intact animals, it is also difficult, if not impossible, to adequately control a wide variety of factors, in addition to glucose delivery, that can influence muscle glucose uptake. For these reasons, it is necessary to use isolated muscle preparations for detailed studies in vitro of the mechanisms by which glucose transport into muscle is regulated.
